This invention relates to N,N'-bis(2,3-dihydroxypropyl)-5-N-(2-hydroxyethyl)glycolamido-2,4,6-triiod oisopthalamide (ioversol).
Ioversol is commonly used as an X-ray contrast agent. The agent may be used in various radiographic procedures including those involving cardiography, coronary arteriography, aortography, cerebral and peripheral angiography, arthrography, intravenous pyelography and urography as well as myelography.
The present commercial manufacture of ioversol proceeds in four steps from bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-aminoisophthalamide to crude ioversol product, which product is subsequently purified. This conversion utilizes two expensive raw materials, acetoxyacetyl chloride (AAC) and bromoethylacetate (BEA), which together contribute to greater than 25% of the final product material cost. Additionally, the present commercial manufacturing process requires the use of several expensive, environmentally undesirable and/or reactive solvents such as 1,1,2-trichloroethane (TCE), dimethylsulfoxide (DMSO) and amylacetate. Each of these solvents have been particularly troublesome in manufacturing due to difficulties in recovery and other operational difficulties. TCE, in particular, is a chlorinated solvent of considerable concern in manufacturing. Thus, there exists a need for an improved process for the manufacture of ioversol which incorporates less expensive and more environmentally suitable raw materials.